O₂-generating MnO₂ nanoparticles for enhanced photodynamic therapy of bladder cancer by ameliorating hypoxia

Abstract

Photodynamic therapy (PDT) is an emerging effective treatment for cancer. However, the great promise of PDT for bladder cancer therapy has not yet been realized because of tumor hypoxia. To address this challenge, we fabricated O2-generating HSA-MnO2-Ce6 NPs (HSA for human serum albumin, Ce6 for chlorin e6, and NPs for nanoparticles) to overcome tumor hypoxia and thus enhance the photodynamic effect for bladder cancer therapy.Methods: The HSA-MnO2-Ce6 NPs were prepared. We investigated the O2 generation of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study, and dual-modal imaging of NPs were demonstrated. Therapeutic efficacy of NPs for bladder cancer was evaluated.Results: HSA-MnO2-Ce6 NPs had an excellent performance in generating O2 in vitro upon reaction with H2O2 at endogenous levels. Moreover, 1O2 generation was increased two-fold by using HSA-MnO2-Ce6 NPs instead of HSA-Ce6 NPs in the presence of H2O2 under 660 nm laser irradiation. In vitro cell viability assays showed that HSA-MnO2-Ce6 NPs themselves were non-toxic but greatly enhanced PDT effects on bladder cancer cells under laser irradiation. In vivo near-infrared (NIR) fluorescence and magnetic resonance (MR) imaging suggested the excellent bladder tumor-targeting property of HSA-MnO2-Ce6 NPs. O2 content in orthotopic bladder cancer was increased 3.5-fold after injection of HSA-MnO2-Ce6 NPs as compared with pre-injection. Given the excellent tumor-targeting ability and negligible toxicity, HSA-MnO2-Ce6 NPs were then used to treat orthotopic bladder cancer by PDT. The PDT with HSA-MnO2-Ce6 NPs showed remarkably improved therapeutic efficacy and significantly prolonged lifetime of mice as compared with controls.Conclusion: This study not only demonstrated the great potential of HSA-MnO2-Ce6 NPs for bladder cancer photodynamic ablation but also provided a new therapeutic strategy to overcoming tumor hypoxia.

Tumor Microenvironment Adaptable Nanoplatform for O2 Self‐Sufficient Chemo/Photodynamic Combination Therapy

“…As we know, MnO 2 could catalyze H 2 O 2 into O 2 for enhanced PDT against hypoxic tumor 41–43. By using dissolve oxygen meter, the generation of O 2 in PMDH solution was quantified after adding H 2 O 2 .…”

Fluorinated Polymer Mediated Transmucosal Peptide Delivery for Intravesical Instillation Therapy of Bladder Cancer

“…In addition to the proof‐of‐principle subcutaneous tumor model, we further studied the antitumor activity of MPI/F‐PEI NPs with an orthotopic bladder cancer model (Figure d), which was built with minimal invasiveness in female BALB/c nude mice following the reported protocol . Briefly, bladder was found and exposed though a small cut made into the skin of the lower abdomen.…”

Gas‐Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy

“…Especially, the O 2 production provided the ROS‐generating sources for enhancing singlet oxygen ( 1 O 2 )‐producing efficacy, which achieved remarkably improved PDT outcome in inhibiting tumor growth as compared to free Ce6 photosensitizers (Figure d,e) . Similarly, Guo and co‐workers synthesized an O 2 ‐generating nanoparticles composed of human serum albumin, Ce6, and MnO 2 for enhanced PDT against orthotopic bladder cancer, which were mainly based on the reaction between MnO 2 component with H 2 O 2 to generate O 2 and subsequently enhanced production efficacy of singlet oxygen . Therefore, these paradigms are typically based on the principle of reactivity of Mn‐based nanoparticles for decomposing H 2 O 2 to produce oxygen.…”